Ulcerative colitis is a chronic, inflammatory disease associated with inflammation of the mucosa of the colon, often starting in the distal portion of the colon, and most frequently affecting individuals ranging in age from 14-40. The most common symptoms are bloody diarrhea accompanied by severe cramps and high fever. Hemorrhage, perforation of the colon, and peripheral arthritis are potential complications. At present neither the cause nor an effective non-surgical method of treating the disease are known. Depending on whether the stage of the disease is classified as mild, moderate, moderately severe, or severe, the strategies for treating it differ. For mild attacks treatment is focused on controlling diarrhea usually with diphenoxylate. Moderate and moderately severe forms of the disease are treated with antibiotics, generally sulfasalazine and/or with corticosteroids respectively. Severe attacks of the disease require hospitalization, drug therapy and in extreme situations colectomy if there is massive hemorrhaging or perforation of the colon. The only known cure for severe ulcerative colitis is complete proctocolectomy, but unfortunately, the patient pays a high price as ileostomy is necessary.
While the cause of ulcerative colitis is unknown several lines of evidence suggest that one or more metabolic by-products secreted by bacteria endogenous to the gut may be responsible. The theory that bacteria are involved has its roots in epidemiological studies which have linked colon cancer to ulcerative colitis. For example, work by Greenstein et al in Gastroenterology, Vol. 77, p. 290 (1979), shows that a high percentage of patients that suffer from ulcerative colitis subsequently develop colon cancer. Because of the association of colon cancer and ulcerative colitis it is probable that both diseases are caused by the same or similar bacterial metabolic by-products.
As discussed by Hill in Cancer, Vol. 36, p. 2387 (1975), colon cancer is thought to be due to metabolic conversion of bile acids into carcinogens by bacteria as the bile acids pass through the colon. The link between bile acids and colon cancer is supported by the observation that the risk of developing colon cancer is greater in people that ingest large amounts of fats. Excessive fat, as discussed by Howell in J. Chronic Dis., Vol. 28, p. 67 (1975), stimulates the production and subsequent secretion of bile acids into the gut. The chemical reactions necessary to carry out the conversion of bile acids into potential carcinogens are known, and have been described by Hill in Cancer, Vol. 36, p. 2387 (1975), and Goddard et al in J. Med. Microbiol., Vol. 8, p. 429 (1975). These reactions require an electron acceptor, and as noted by Goddard et al in J. Med. Microbiol., Vol. 8, p. 429 (1975), the likely candidate in the colon is Vitamin K. Thus, it should be possible to prevent both ulcerative colitis and colon cancer by administering to patients drugs that antagonize the effects of Vitamin K.